STEP 1: Research Study Investigating How Well Semaglutide Works in People Suffering From Overweight or Obesity

Overweight or Obesity Clinical Trial

— STEP 1  

Official title:

Effect and Safety of Semaglutide 2.4 mg Once-weekly in Subjects With Overweight or Obesity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03548935
• Other study ID #: NN9536-4373
• Secondary ID: U1111-1200-80532
• Status: Completed
• Phase: Phase 3
• Start date: June 4, 2018
• Est. completion date: March 5, 2021

Study information

• Verified date: November 2021
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will look at the change in participants' body weight from the start to the end of the study. The weight loss in participants taking semaglutide (a new medicine) will be compared to the weight loss of participants taking "dummy" medicine. In addition to taking the medicine, participants will have talks with study staff about healthy food choices, how to be more physically active and what you can do to lose weight. Participants will either get semaglutide or "dummy" medicine - which treatment participants get, is decided by chance. Participants will need to take 1 injection once a week. The study medicine is injected with a thin needle in a skin fold in the stomach, thigh or upper arm. The study has two phases: A main phase and an extension phase.The main phase will last for about 1.5 years. Participants will have 15 clinic visits and 10 phone calls with the study doctor. Extension phase: Approximately 300 participants will continue in the extension phase in the following countries only: Canada, Germany, the UK and selected sites in the US and Japan. These participants will be in the study for about 2.5 years.They will not receive treatment, but will attend another 5 follow-up visits with the study doctor.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1961
• Est. completion date: March 5, 2021
• Est. primary completion date: March 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Main phase:

• Male or female, age greater than or equal to 18 years at the time of signing informed consent

• Body mass index (BMI) greater than or equal to 30.0 kg/sqm or greater than or equal to 27.0 kg/sqm with the presence of at least one of the following weight-related comorbidities (treated or untreated): hypertension, dyslipidaemia, obstructive sleep apnoea or cardiovascular disease

• History of at least one self-reported unsuccessful dietary effort to lose body weight

Extension phase:

• Informed consent for the extension phase obtained before any trial related activities for the extension phase

• On randomised treatment on the target dose at week 68, i.e. treated with 2.4 mg semaglutide once-weekly or semaglutide placebo

Exclusion Criteria:

Main phase:

• Glycated haemoglobin (HbA1C) greater than or equal to 48 mmol/mol (6.5%) as measured by the central laboratory at screening

• A self-reported change in body weight greater than 5 kg (11 lbs) within 90 days before screening irrespective of medical records

Extension phase:

• Female who is pregnant or intends to become pregnant during the extension phase

• Any disorder, unwillingness or inability, not covered by any of the other exclusion criteria, which in the investigator's opinion, might jeopardise the subject's compliance with the extension of the trial

Related Conditions & MeSH terms

• Metabolism and Nutrition Disorder
• Nutrition Disorders
• Obesity
• Overweight
• Overweight or Obesity

Intervention

Drug:
• Semaglutide
Participants will receive semaglutide subcutaneous (s.c.; under the skin) injection(s) once-weekly as well as diet and physical activity counselling for 68 weeks. Dose escalation of semaglutide will take place as follows: 0.25 mg from week 1 to 4, 0.5 mg from week 5 to 8, 1.0 mg from week 9 to 12, 1.7 mg from week 13 to 16 and 2.4 mg from week 17 to week 68.
• Placebo (semaglutide)
Participants will receive semaglutide matching placebo s.c. injection(s) once-weekly as well as diet and physical activity counselling for 68 weeks.

Locations

Country	Name	City	State
Argentina	Novo Nordisk Investigational Site	Caba
Argentina	Novo Nordisk Investigational Site	Ciudad de Buenos Aires
Argentina	Novo Nordisk Investigational Site	Córdoba
Argentina	Novo Nordisk Investigational Site	Corrientes
Argentina	Novo Nordisk Investigational Site	Santa Rosa
Belgium	Novo Nordisk Investigational Site	Boussu
Belgium	Novo Nordisk Investigational Site	Bruxelles
Belgium	Novo Nordisk Investigational Site	Edegem
Belgium	Novo Nordisk Investigational Site	Leuven
Belgium	Novo Nordisk Investigational Site	Liège
Bulgaria	Novo Nordisk Investigational Site	Plovdiv
Bulgaria	Novo Nordisk Investigational Site	Sofia
Bulgaria	Novo Nordisk Investigational Site	Sofia
Bulgaria	Novo Nordisk Investigational Site	Sofia
Canada	Novo Nordisk Investigational Site	Edmonton	Alberta
Canada	Novo Nordisk Investigational Site	Hamilton	Ontario
Canada	Novo Nordisk Investigational Site	North York	Ontario
Canada	Novo Nordisk Investigational Site	Quebec
Canada	Novo Nordisk Investigational Site	Quebec
Canada	Novo Nordisk Investigational Site	Surrey	British Columbia
Canada	Novo Nordisk Investigational Site	Toronto	Ontario
Denmark	Novo Nordisk Investigational Site	Aarhus N
Finland	Novo Nordisk Investigational Site	Oulu
Finland	Novo Nordisk Investigational Site	University Of Helsinki
France	Novo Nordisk Investigational Site	Le Coudray
France	Novo Nordisk Investigational Site	Narbonne
France	Novo Nordisk Investigational Site	Paris
France	Novo Nordisk Investigational Site	PARIS cedex 13
France	Novo Nordisk Investigational Site	Pessac
France	Novo Nordisk Investigational Site	Pierre Benite
France	Novo Nordisk Investigational Site	Venissieux
Germany	Novo Nordisk Investigational Site	Berlin
Germany	Novo Nordisk Investigational Site	Bochum
Germany	Novo Nordisk Investigational Site	Essen
Germany	Novo Nordisk Investigational Site	Essen
Germany	Novo Nordisk Investigational Site	Falkensee
Germany	Novo Nordisk Investigational Site	Frankfurt
Germany	Novo Nordisk Investigational Site	Giessen
Germany	Novo Nordisk Investigational Site	Hamburg
Germany	Novo Nordisk Investigational Site	Hohenmölsen
Germany	Novo Nordisk Investigational Site	Leipzig
Germany	Novo Nordisk Investigational Site	Saint Ingbert-Oberwürzbach
Germany	Novo Nordisk Investigational Site	Stuttgart
Germany	Novo Nordisk Investigational Site	Wangen
India	Novo Nordisk Investigational Site	Chennai	Tamil Nadu
India	Novo Nordisk Investigational Site	Guntur	Andhra Pradesh
India	Novo Nordisk Investigational Site	Hyderabad
India	Novo Nordisk Investigational Site	Kolkata	West Bengal
India	Novo Nordisk Investigational Site	Ludhiana
India	Novo Nordisk Investigational Site	Nagpur	Maharashtra
India	Novo Nordisk Investigational Site	New Dehli	New Delhi
India	Novo Nordisk Investigational Site	Pune	Maharashtra
India	Novo Nordisk Investigational Site	Pune	Maharashtra
India	Novo Nordisk Investigational Site	Rohtak	Haryana
India	Novo Nordisk Investigational Site	Secunderabad,	Andhra Pradesh
India	Novo Nordisk Investigational Site	Surat	Gujarat
India	Novo Nordisk Investigational Site	Thiruvananthapuram	Kerala
Japan	Novo Nordisk Investigational Site	Chiba-shi, Chiba
Japan	Novo Nordisk Investigational Site	Suita-shi, Osaka
Japan	Novo Nordisk Investigational Site	Tokyo
Japan	Novo Nordisk Investigational Site	Tokyo
Japan	Novo Nordisk Investigational Site	Tokyo
Mexico	Novo Nordisk Investigational Site	Guadalajara	Jalisco
Mexico	Novo Nordisk Investigational Site	Hermosillo	Sonora
Mexico	Novo Nordisk Investigational Site	Merida	Yucatan
Poland	Novo Nordisk Investigational Site	Gdynia
Poland	Novo Nordisk Investigational Site	Lodz
Poland	Novo Nordisk Investigational Site	Poznan
Poland	Novo Nordisk Investigational Site	Szczecin
Puerto Rico	Novo Nordisk Investigational Site	San Juan
Russian Federation	Novo Nordisk Investigational Site	Moscow
Russian Federation	Novo Nordisk Investigational Site	Novosibirsk
Russian Federation	Novo Nordisk Investigational Site	Novosibirsk
Russian Federation	Novo Nordisk Investigational Site	Penza
Russian Federation	Novo Nordisk Investigational Site	Saint-Petersburg
Russian Federation	Novo Nordisk Investigational Site	Tomsk
Russian Federation	Novo Nordisk Investigational Site	Voronezh
Russian Federation	Novo Nordisk Investigational Site	Yaroslavl
Taiwan	Novo Nordisk Investigational Site	Taipei
United Kingdom	Novo Nordisk Investigational Site	Bristol
United Kingdom	Novo Nordisk Investigational Site	Cambridge
United Kingdom	Novo Nordisk Investigational Site	Coventry
United Kingdom	Novo Nordisk Investigational Site	Glasgow
United Kingdom	Novo Nordisk Investigational Site	Liverpool
United Kingdom	Novo Nordisk Investigational Site	London
United Kingdom	Novo Nordisk Investigational Site	London
United Kingdom	Novo Nordisk Investigational Site	Norwich
United Kingdom	Novo Nordisk Investigational Site	Rotherham
United Kingdom	Novo Nordisk Investigational Site	Taunton
United States	Novo Nordisk Investigational Site	Anaheim	California
United States	Novo Nordisk Investigational Site	Anniston	Alabama
United States	Novo Nordisk Investigational Site	Aurora	Colorado
United States	Novo Nordisk Investigational Site	Austin	Texas
United States	Novo Nordisk Investigational Site	Bountiful	Utah
United States	Novo Nordisk Investigational Site	Buckley	Michigan
United States	Novo Nordisk Investigational Site	Butte	Montana
United States	Novo Nordisk Investigational Site	Charleston	South Carolina
United States	Novo Nordisk Investigational Site	Chicago	Illinois
United States	Novo Nordisk Investigational Site	Chicago	Illinois
United States	Novo Nordisk Investigational Site	Chiefland	Florida
United States	Novo Nordisk Investigational Site	Crystal River	Florida
United States	Novo Nordisk Investigational Site	Dallas	Texas
United States	Novo Nordisk Investigational Site	Dallas	Texas
United States	Novo Nordisk Investigational Site	Dallas	Texas
United States	Novo Nordisk Investigational Site	Indianapolis	Indiana
United States	Novo Nordisk Investigational Site	Jacksonville	Florida
United States	Novo Nordisk Investigational Site	Jacksonville	Florida
United States	Novo Nordisk Investigational Site	Lomita	California
United States	Novo Nordisk Investigational Site	Louisville	Kentucky
United States	Novo Nordisk Investigational Site	Nashville	Tennessee
United States	Novo Nordisk Investigational Site	Ocala	Florida
United States	Novo Nordisk Investigational Site	Omaha	Nebraska
United States	Novo Nordisk Investigational Site	Panama City	Florida
United States	Novo Nordisk Investigational Site	Plantation	Florida
United States	Novo Nordisk Investigational Site	Ponte Vedra	Florida
United States	Novo Nordisk Investigational Site	Renton	Washington
United States	Novo Nordisk Investigational Site	Richmond	Virginia
United States	Novo Nordisk Investigational Site	Rochester	New York
United States	Novo Nordisk Investigational Site	Roswell	Georgia
United States	Novo Nordisk Investigational Site	Round Rock	Texas
United States	Novo Nordisk Investigational Site	Saint Peters	Missouri
United States	Novo Nordisk Investigational Site	Salisbury	North Carolina
United States	Novo Nordisk Investigational Site	Simpsonville	South Carolina
United States	Novo Nordisk Investigational Site	Spring Valley	California
United States	Novo Nordisk Investigational Site	Topeka	Kansas
United States	Novo Nordisk Investigational Site	Waterbury	Connecticut
United States	Novo Nordisk Investigational Site	West Reading	Pennsylvania
United States	Novo Nordisk Investigational Site	Wilmington	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Bulgaria,  Canada,  Denmark,  Finland,  France,  Germany,  India,  Japan,  Mexico,  Poland,  Puerto Rico,  Russian Federation,  Taiwan,  United Kingdom, 

References & Publications (2)

Kushner RF, Calanna S, Davies M, Dicker D, Garvey WT, Goldman B, Lingvay I, Thomsen M, Wadden TA, Wharton S, Wilding JPH, Rubino D. Semaglutide 2.4 mg for the Treatment of Obesity: Key Elements of the STEP Trials 1 to 5. Obesity (Silver Spring). 2020 Jun;28(6):1050-1061. doi: 10.1002/oby.22794. — View Citation

Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, McGowan BM, Rosenstock J, Tran MTD, Wadden TA, Wharton S, Yokote K, Zeuthen N, Kushner RF; STEP 1 Study Group. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J M — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Body Weight (%)	Change in body weight from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from both in-trial and on-treatment observation periods. In-trial observation period: the uninterrupted time interval from date of randomization (week 0) to date of last contact with trial site (week 75). On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68), including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).	Baseline (week 0) to week 68
Primary	Participants Who Achieve 5 or More Percent Body Weight Reduction (Yes/no)	Number of participants who achieved weight loss more than or equal to 5% (yes/no) at week 68 are presented. The endpoint was evaluated based on the data from both in-trial and on-treatment observation periods. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75). On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68), including 2 weeks of follow-up. It excludes any period of temporary treatment interruption.	After week 68
Secondary	Subjects Who Achieve 10 or More Percent Body Weight Reduction (Yes/no)	Number of participants who achieved weight loss more than or equal to (=) 10% at week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from date of randomization (week 0) to date of last contact with trial site (week 75).	Week 68
Secondary	Participants Who Achieve 15 or More Percent Body Weight Reduction (Yes/no)	Number of participants who achieved more than or equal to (=) 15% weight loss at week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).	Week 68
Secondary	Participants Who Achieve 20 or More Percent Body Weight Reduction (Yes/no)	Number of participants who achieved more than or equal to (=) 20% weight loss at week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).	Week 68
Secondary	Change in Waist Circumference (cm)	Change in waist circumference from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to date of last contact with trial site (week 75).	Baseline (week 0) to week 68
Secondary	Change in Systolic Blood Pressure (mmHg)	Change in systolic blood pressure from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to date of last contact with trial site (week 75).	Baseline (week 0) to week 68
Secondary	Change in Short Form 36 (SF-36)	SF-36 is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2™ questionnaire measured eight domains of functional health and well-being as well as two component summary scores (physical component summary and mental component summary). In the metric of norm-based scores, 50 and 10 corresponds to the mean and standard deviation, respectively, for the 2009 US general population. Change from week 0 in the domain scores and component summary scores were evaluated at week 68. A positive change score indicates an improvement since baseline. These endpoints were evaluated based on the data from in-trial observation period which is the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).	Baseline (week 0) to week 68
Secondary	Change in Impact of Weight on Quality of Life-Lite for Clinical Trial (IWQoL-Lite for CT) Score	IWQoL-Lite for CT is a modified version of an instrument designed to assess weight-related quality of life. It is used to assess the impact of body weight changes on patients' physical and psychosocial functioning in three composite scores (physical function, physical and psychosocial) and a total score. The scores range between 0-100 where higher scores indicate a better quality of life. A positive change score indicates an improvement since baseline. These endpoints were evaluated based on the data from in-trial observation period which is the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).	Baseline (week 0) to week 68
Secondary	Change in Body Weight (kg)	Change in body weight from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).	Baseline (week 0) to week 68
Secondary	Change in Body Mass Index (BMI) (kg/m2)	Change in body mass index from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).	Baseline (week 0) to week 68
Secondary	Change in HbA1C (%)	Change in glycosylated haemoglobin (HbA1c) from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).	Baseline (week 0) to week 68
Secondary	Change in HbA1C (mmol/Mol)	Change in HbA1c from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).	Baseline (week 0) to week 68
Secondary	Change in Fasting Plasma Glucose (FPG) (mg/dL)	Change in fasting plasma glucose from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).	Baseline (week 0) to week 68
Secondary	Change in Fasting Serum Insulin (mIU/L) - Ratio to Baseline	Change in fasting serum insulin from week 0 to week 68 is presented as ratio to baseline. Fasting serum insulin was measured in milli-international units per milliliter (mIU/mL). The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).	Baseline (week 0) to week 68
Secondary	Change in Diastolic Blood Pressure (mmHg)	Change in diastolic blood pressure from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).	Baseline (week 0) to week 68
Secondary	Change in Total Cholesterol (mg/dL) - Ratio to Baseline	Change in fasting total cholesterol from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).	Baseline (week 0) to week 68
Secondary	Change in High-density Lipoproteins (HDL) (mg/dL) - Ratio to Baseline	Change in fasting HDL from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).	Baseline (week 0) to week 68
Secondary	Change in Low-density Lipoproteins (LDL) (mg/dL) - Ratio to Baseline	Change in fasting LDL from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).	Baseline (week 0) to week 68
Secondary	Change in Very Low-density Lipoproteins (VLDL) (mg/dL) - Ratio to Baseline	Change in fasting VLDL from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).	Baseline (week 0) to week 68
Secondary	Change in Free Fatty Acids (mg/dL) - Ratio to Baseline	Change in fasting free fatty acids from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).	Baseline (week 0) to week 68
Secondary	Change in Triglycerides (mg/dL) - Ratio to Baseline	Change in fasting triglycerides from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).	Baseline (week 0) to week 68
Secondary	Change in High Sensitivity C-Reactive Protein (hsCRP) - (mg/L) - Ratio to Baseline	Change in high sensitivity C-reactive protein from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).	Baseline (week 0) to week 68
Secondary	Change in Plasminogen Activator Inhibitor-1 (PAI-1) Activity (AU/ml) - Ratio to Baseline	Change in plasminogen activator inhibitor-1 activity from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).	Baseline (week 0) to week 68
Secondary	Change in Soluble Leptin Receptor (ng/mL) - Ratio to Baseline	Change in soluble leptin receptor from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).	Baseline (week 0) to week 68
Secondary	Change in Leptin (ng/mL) - Ratio to Baseline	Change in leptin from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).	Baseline (week 0) to week 68
Secondary	Change in Body Composition (Total Fat Mass) (%)	Change in body composition (total fat mass) from baseline (week 0) to week 68 is presented. Body composition was assessed using Dual Energy X-ray Absorpmetry (DEXA). The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).	Baseline (week 0) to week 68
Secondary	Change in Body Composition (Total Fat Mass) (kg)	Change in body composition (total fat mass) from baseline (week 0) to week 68 is presented. Body composition was assessed using Dual Energy X-ray Absorpmetry (DEXA). The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).	Baseline (week 0) to week 68
Secondary	Change in Body Composition (Lean Body Mass) (%)	Change in body composition (lean body mass) from baseline (week 0) to week 68 is presented. Body composition was assessed using DEXA. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).	Baseline (week 0) to week 68
Secondary	Change in Body Composition (Lean Body Mass) (kg)	Change in body composition (lean body mass) from baseline (week 0) to week 68 is presented. Body composition was assessed using DEXA. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).	Baseline (week 0) to week 68
Secondary	Change in Body Composition (Visceral Fat Mass) (%)	Change in body composition (visceral fat mass) from baseline (week 0) to week 68 is presented. Body composition was assessed using DEXA. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).	Baseline (week 0) to week 68
Secondary	Change in Body Composition (Visceral Fat Mass) (kg)	Change in body composition (visceral fat mass) from baseline (week 0) to week 68 is presented. Body composition was assessed using DEXA. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).	Baseline (week 0) to week 68
Secondary	Change in Body Weight (%) - DEXA Subpopulation	Change in body weight from baseline (week 0) to week 68 is presented in DEXA subpopulation. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).	Baseline (week 0) to week 68
Secondary	Change in Body Weight (kg) - DEXA Subpopulation	Change in body weight from baseline (week 0) to week 68 is presented in DEXA subpopulation. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).	Baseline (week 0) to week 68
Secondary	Participants Who Achieve "Responder Definition Value" (Yes/no) for SF-36 Physical Functioning Score	The observed number of participants experiencing a meaningful within participant improvement in SF-36 Physical function after 68 weeks was determined based on two different thresholds. The threshold of 4.3 is the default generic responder threshold defined in SF-36 manual for a general population. The threshold of 3.7 is specific for the population with overweight or obesity included in the study and calculated using patient global rating anchor questionnaires to reflect participants' own perspective based on FDA recommendations. In the reported data, "Yes" infers the number of participants who have achieved an improvement in score greater than or equal to the threshold and "No" infers number of participants who have not achieved an improvement in score greater than or equal to the threshold. The endpoint was evaluated based on the in-trial observation period which is the uninterrupted time interval from randomization (week 0) to last trial related subject-site contact (week 75).	After week 68
Secondary	Participants Who Achieve "Responder Definition Value" (Yes/no) for IWQoL-Lite for CT Physical Function Domain (5-items) Score	The observed number of participants experiencing a meaningful within participant improvement in IWQOL-Lite-CT physical function after 68 weeks was determined based on two different thresholds. The threshold of 20 was a preliminary responder threshold based on earlier studies. The threshold of 14.6 is specific for the population with overweight or obesity included in the study and calculated using patient global rating anchor questionnaires to reflect participants' own perspective based on FDA recommendations. In the reported data, "Yes" infers the number of participants who have achieved an improvement in score greater than or equal to the threshold and "No" infers the number of participants who have not achieved an improvement in score greater than or equal to the threshold. The endpoint was evaluated based on the in-trial observation period. In trial observation period: the uninterrupted time interval from randomization (week 0) to last trial related subject-site contact (week 75).	After week 68
Secondary	Number of Treatment Emergent Adverse Events (TEAEs)	An adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a product, whether or not considered related to the product. All AEs mentioned here are treatment emergent adverse events (TEAE) defined as an event for which the onset of the event occurs in the on-treatment period. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68), including 7 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 7 consecutive missed doses (off-treatment period).	Baseline (week 0) to week 75
Secondary	Number of Serious Adverse Events (SAEs)	A serious adverse event (SAE) is defined as any untoward medical occurrence that at any dose results in death, or is life-threatening, or requires inpatient hospitalization or causes prolongation of existing hospitalization results in persistent or significant disability/incapacity, or may have caused a congenital anomaly/birth defect, or requires intervention to prevent permanent impairment or damage. The SAEs occurred from week 0 to week 75 is presented. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68), including 7 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 7 consecutive missed doses (off-treatment period).	Baseline (week 0) to week 75
Secondary	Change in Pulse	Change in pulse from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68) including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).	Baseline (week 0) to week 68
Secondary	Change in Amylase - Ratio to Baseline	Change in amylase (measured as units per litre [U/L]) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68) including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).	Baseline (week 0) to week 68
Secondary	Change in Lipase - Ratio to Baseline	Change in lipase (measured as units per litre [U/L]) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68) including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).	Baseline (week 0) to week 68
Secondary	Change in Calcitonin - Ratio to Baseline	Change in calcitonin (measured as ng/L) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68) including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).	Baseline (week 0) to week 68